AGBT talk: Maria Mendez-Lago, BC Cancer Agency

Title: Mutations in MLL2 and MEF2B Genes in Follicular Lymphoma and Diffuse Large B-Cell Lymphoma.

Background on Follicular Lympoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL)- most common types of Non Hodgkin lymphoma

Goal: Detect driver mutations, characerize the pattern of mutations, and then understand the role of the mutations in the proteins in which they occur.

Method: 119 lymphoma samples were sequenced: genome/transcriptome. hg18  exon-exon junctions, SNVmix SNV calls.

Result: 137 genes with 1 confirmed somatic mutations  with mutations in at least 2 other samples.

Discovered an enrichment for histone modifying genes.  These turn transcription on and off in the normal cell.

To get a better picture, MLL2 locus was sequenced in several 10’s of lymphomas, as well as 8 normal samples.  MLL2 is highly mutated in lymphoma: FL 89%, DLBCL: 32%, DLBCL cell lines: 59%, Healthy BCells: 0%.

RNA-seq missed 33 mutations –

  • 20 were indels. (Missed by SNV calling methods.)
  • 3 were in splice sites
  • 10 new non synonymous SNVs in regions previously low coverage. (eg, the transcriptome contained low amounts of this gene.)

Very pretty image of the distribution of mutations in MLL2.

Assembly was done with Trans-ABYSS to confirm effect of a mutation at a donor site, as well we RT-PCR + Sanger.

Some samples had 2 independent mutations in MLL2 (one in each allele).

For other gene, MEF2B, targeted sequencing was used, as the mutations were mainly localized to a single mutation.  Some were outside, so capture strategy was used (Biotinylated RNA baits.)  captured RNA were sequenced on a GAII.

There were a few common mutations, and most mutations were found in exon 3 and 2.

[first time I’ve seen this today:] crystal structure used to show location of most common mutations, and why they interfere in binding.


There are several genes frequently mutated in FL and DBCL.  MLL2 and MEF2B are common in lymphomas at reasonably high levels and are likely strong drivers in lymphoma.

[I believe this has all been published already [EDIT: NO, it hasn’t – my apologies! And I’m that much more impressed that we’ve been allowed to blog this presentation!], but a great talk, none-the-less.  A very concise and clear explanation of the mutations found and why they are important.]

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